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Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Adults With Chronic Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV)-1 Coinfection (ASTRAL-5)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02480712
Recruitment Status : Completed
First Posted : June 24, 2015
Results First Posted : June 1, 2017
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis C Virus Infection
Intervention Drug: SOF/VEL
Enrollment 107
Recruitment Details Participants were enrolled at 17 study sites in the United States. The first participant was screened on 01 July 2015. The last study visit occurred on 22 June 2016.
Pre-assignment Details 149 participants were screened.
Arm/Group Title SOF/VEL 12 Weeks
Hide Arm/Group Description Sofosbuvir/velpatasvir (SOF/VEL; Epclusa®) (400/100 mg) fixed-dose combination (FDC) tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1
Period Title: Overall Study
Started 107
Completed 96
Not Completed 11
Reason Not Completed
Enrolled but Never Treated             1
Lost to Follow-up             5
Withdrew Consent             3
Death             1
Lack of Efficacy             1
Arm/Group Title SOF/VEL 12 Weeks
Hide Arm/Group Description SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1
Overall Number of Baseline Participants 106
Hide Baseline Analysis Population Description
Safety Analysis Set: Participants who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 106 participants
54  (9.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants
Female
15
  14.2%
Male
91
  85.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Black or African American Number Analyzed 106 participants
48
  45.3%
White Number Analyzed 106 participants
54
  50.9%
Asian Number Analyzed 106 participants
3
   2.8%
Other Number Analyzed 106 participants
1
   0.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 106 participants
15
  14.2%
Not Hispanic or Latino Number Analyzed 106 participants
91
  85.8%
IL28b Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants
CC
24
  22.6%
CT
52
  49.1%
TT
30
  28.3%
[1]
Measure Description: The CC, CT, and TT alleles are different forms of the IL28b gene.
HCV RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 106 participants
6.3  (0.57)
HCV RNA Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants
< 800,000 IU/mL
28
  26.4%
≥ 800,000 IU/mL
78
  73.6%
HIV RNA category   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Boosted TDF Containing Regimens Number Analyzed 56 participants
HIV RNA < 50 copies/mL
55
  98.2%
HIV RNA ≥ 50 copies/mL
1
   1.8%
Non-Boosted TDF Containing Regimens Number Analyzed 35 participants
HIV RNA < 50 copies/mL
35
 100.0%
HIV RNA ≥ 50 copies/mL
0
   0.0%
Non TDF Containing Regimens Number Analyzed 15 participants
HIV RNA < 50 copies/mL
14
  93.3%
HIV RNA ≥ 50 copies/mL
1
   6.7%
[1]
Measure Analysis Population Description:

Participants in the Safety Analysis Set were analyzed by tenofovir disoproxil fumarate(TDF)-containing antiretroviral therapy (ART) at baseline:

  • Boosted TDF-containing regimens
  • Non-boosted TDF-containing regimens
  • Non TDF-containing regimens
Serum Creatinine   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Boosted TDF Containing Regimens Number Analyzed 56 participants
1.02  (0.194)
Non-Boosted TDF Containing Regimens Number Analyzed 35 participants
0.98  (1.44)
Non TDF Containing Regimens Number Analyzed 15 participants
1.02  (0.255)
[1]
Measure Analysis Population Description:

Participants in the Safety Analysis Set were analyzed by TDF-containing ART at baseline:

  • Boosted TDF-containing regimens
  • Non-boosted TDF-containing regimens
  • Non TDF-containing regimens
1.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
Hide Description SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
Time Frame Posttreatment Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All enrolled participants who received at least one dose of study drug.
Arm/Group Title SOF/VEL 12 Weeks
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1
Overall Number of Participants Analyzed 106
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
95.3
(89.3 to 98.5)
2.Primary Outcome
Title Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Hide Description [Not Specified]
Time Frame Up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title SOF/VEL 12 Weeks
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1
Overall Number of Participants Analyzed 106
Measure Type: Number
Unit of Measure: percentage of participants
1.9
3.Secondary Outcome
Title Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Hide Description SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Time Frame Posttreatment Weeks 4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title SOF/VEL 12 Weeks
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1
Overall Number of Participants Analyzed 106
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
SVR4
95.3
(89.3 to 98.5)
SVR24
95.3
(89.3 to 98.5)
4.Secondary Outcome
Title Percentage of Participants With HCV RNA < LLOQ on Treatment
Hide Description [Not Specified]
Time Frame Up to 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title SOF/VEL 12 Weeks
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1
Overall Number of Participants Analyzed 106
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 1 Number Analyzed 105 participants
25.7
(17.7 to 35.2)
Week 2 Number Analyzed 103 participants
68.0
(58.0 to 76.8)
Week 4 Number Analyzed 103 participants
92.2
(85.3 to 96.6)
Week 6 Number Analyzed 103 participants
99.0
(94.7 to 100.0)
Week 8 Number Analyzed 102 participants
100.0
(96.4 to 100.0)
Week 10 Number Analyzed 102 participants
100.0
(96.4 to 100.0)
Week 12 Number Analyzed 102 participants
100.0
(96.4 to 100.0)
5.Secondary Outcome
Title HCV RNA Change From Baseline/Day 1
Hide Description [Not Specified]
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title SOF/VEL 12 Weeks
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1
Overall Number of Participants Analyzed 106
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
Change at Week 1 Number Analyzed 101 participants
-4.47  (0.606)
Change at Week 2 Number Analyzed 101 participants
-4.97  (0.577)
Change at Week 4 Number Analyzed 102 participants
-5.15  (0.560)
Change at Week 6 Number Analyzed 103 participants
-5.18  (0.572)
Change at Week 8 Number Analyzed 102 participants
-5.17  (0.575)
Change at Week 10 Number Analyzed 102 participants
-5.17  (0.575)
Change at Week 12 Number Analyzed 102 participants
-5.17  (0.575)
6.Secondary Outcome
Title Percentage of Participants With Virologic Failure
Hide Description

Virologic failure was defined as:

  • On-treatment virologic failure:

    • Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or
    • Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
    • Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)
  • Virologic relapse:

    • Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit
Time Frame Up to Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title SOF/VEL 12 Weeks
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1
Overall Number of Participants Analyzed 106
Measure Type: Number
Unit of Measure: percentage of participants
1.9
7.Secondary Outcome
Title Percentage of Participants That Maintained HIV-1 RNA < 50 Copies/mL While On HCV Treatment
Hide Description [Not Specified]
Time Frame Up to 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed by TDF-containing ART at baseline:

  • Boosted TDF-containing regimens
  • Non-boosted TDF-containing regimens
  • Non TDF-containing regimens
Arm/Group Title SOF/VEL 12 Weeks (Boosted TDF Containing Regimens) SOF/VEL 12 Weeks (Non-Boosted TDF Containing Regimens) SOF/VEL 12 Weeks (Non TDF Containing Regimens)
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1. Data for participants who took boosted TDF-containing regimens (defined as regimens containing TDF and ritonavir (RTV) or cobicistat (COBI)-boosted protease inhibitors (PIs) or other agents (eg, elvitegravir (EVG)/COBI)) are summarized in this group.
SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1. Data are summarized for participants who took non-boosted TDF-containing regimens (defined as regimens containing TDF and non-RTV or COBI-boosted PIs or other agents).
SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1. Data are summarized for participants taking regimens that do not contain TDF.
Overall Number of Participants Analyzed 56 35 15
Measure Type: Number
Unit of Measure: percentage of participants
Week 4 Number Analyzed 54 participants 35 participants 14 participants
94.4 97.1 100
Week 8 Number Analyzed 54 participants 35 participants 14 participants
96.3 97.1 100
Week 12 Number Analyzed 53 participants 35 participants 14 participants
96.2 100 92.9
8.Secondary Outcome
Title Serum Creatinine Change From Baseline At the End of Treatment and At Posttreatment Week 12
Hide Description [Not Specified]
Time Frame Week 12; Posttreatment Week 12
Hide Outcome Measure Data
Hide Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed by TDF-containing ART at baseline:

  • Boosted TDF-containing regimens
  • Non-boosted TDF-containing regimens
  • Non TDF-containing regimens
Arm/Group Title SOF/VEL 12 Weeks (Boosted TDF Containing Regimens) SOF/VEL 12 Weeks (Non-Boosted TDF Containing Regimens) SOF/VEL 12 Weeks (Non TDF Containing Regimens)
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1. Data for participants who took boosted TDF-containing regimens (defined as regimens containing TDF and RTV or COBI-boosted PIs or other agents (eg, EVG/COBI)) are summarized in this group.
SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1. Data are summarized for participants who took non-boosted TDF-containing regimens (defined as regimens containing TDF and non-RTV or COBI-boosted PIs or other agents).
SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1. Data are summarized for participants taking regimens that do not contain TDF.
Overall Number of Participants Analyzed 56 35 15
Mean (Standard Deviation)
Unit of Measure: mg/dL
Change at Week 12 Number Analyzed 51 participants 35 participants 14 participants
0.09  (0.196) 0.04  (0.107) 0.00  (0.083)
Change at Posttreatment Week 12 Number Analyzed 53 participants 35 participants 12 participants
0.04  (0.153) 0.02  (0.142) -0.06  (0.204)
Time Frame Up to 12 Weeks Plus 30 Days
Adverse Event Reporting Description Safety Analysis Set
 
Arm/Group Title SOF/VEL 12 Weeks (Boosted TDF Containing Regimens) SOF/VEL 12 Weeks (Non-Boosted TDF Containing Regimens) SOF/VEL 12 Weeks (Non TDF Containing Regimens)
Hide Arm/Group Description SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1. Data for participants who took boosted TDF-containing regimens (defined as regimens containing TDF and RTV or COBI-boosted PIs or other agents (eg, EVG/COBI)) are summarized in this group. SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1. Data are summarized for participants who took non-boosted TDF-containing regimens (defined as regimens containing TDF and non-RTV or COBI-boosted PIs or other agents). SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1. Data are summarized for participants taking regimens that do not contain TDF.
All-Cause Mortality
SOF/VEL 12 Weeks (Boosted TDF Containing Regimens) SOF/VEL 12 Weeks (Non-Boosted TDF Containing Regimens) SOF/VEL 12 Weeks (Non TDF Containing Regimens)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
SOF/VEL 12 Weeks (Boosted TDF Containing Regimens) SOF/VEL 12 Weeks (Non-Boosted TDF Containing Regimens) SOF/VEL 12 Weeks (Non TDF Containing Regimens)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/56 (3.57%)   0/35 (0.00%)   0/15 (0.00%) 
Infections and infestations       
Localised infection  1  1/56 (1.79%)  0/35 (0.00%)  0/15 (0.00%) 
Sepsis  1  1/56 (1.79%)  0/35 (0.00%)  0/15 (0.00%) 
Urinary tract infection bacterial  1  1/56 (1.79%)  0/35 (0.00%)  0/15 (0.00%) 
Nervous system disorders       
Radial nerve palsy  1  1/56 (1.79%)  0/35 (0.00%)  0/15 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SOF/VEL 12 Weeks (Boosted TDF Containing Regimens) SOF/VEL 12 Weeks (Non-Boosted TDF Containing Regimens) SOF/VEL 12 Weeks (Non TDF Containing Regimens)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   34/56 (60.71%)   19/35 (54.29%)   9/15 (60.00%) 
Gastrointestinal disorders       
Abdominal distension  1  3/56 (5.36%)  2/35 (5.71%)  0/15 (0.00%) 
Constipation  1  2/56 (3.57%)  2/35 (5.71%)  0/15 (0.00%) 
Diarrhoea  1  6/56 (10.71%)  2/35 (5.71%)  0/15 (0.00%) 
Nausea  1  4/56 (7.14%)  2/35 (5.71%)  1/15 (6.67%) 
Toothache  1  0/56 (0.00%)  0/35 (0.00%)  1/15 (6.67%) 
Vomiting  1  1/56 (1.79%)  1/35 (2.86%)  1/15 (6.67%) 
General disorders       
Chest discomfort  1  0/56 (0.00%)  1/35 (2.86%)  1/15 (6.67%) 
Fatigue  1  16/56 (28.57%)  7/35 (20.00%)  3/15 (20.00%) 
Immune system disorders       
Seasonal allergy  1  0/56 (0.00%)  2/35 (5.71%)  0/15 (0.00%) 
Infections and infestations       
Bronchitis  1  3/56 (5.36%)  0/35 (0.00%)  0/15 (0.00%) 
Fungal infection  1  0/56 (0.00%)  0/35 (0.00%)  1/15 (6.67%) 
Nasopharyngitis  1  3/56 (5.36%)  2/35 (5.71%)  0/15 (0.00%) 
Upper respiratory tract infection  1  8/56 (14.29%)  1/35 (2.86%)  0/15 (0.00%) 
Urinary tract infection  1  2/56 (3.57%)  0/35 (0.00%)  2/15 (13.33%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  6/56 (10.71%)  1/35 (2.86%)  1/15 (6.67%) 
Back pain  1  0/56 (0.00%)  2/35 (5.71%)  0/15 (0.00%) 
Flank pain  1  0/56 (0.00%)  0/35 (0.00%)  1/15 (6.67%) 
Muscle spasms  1  1/56 (1.79%)  0/35 (0.00%)  1/15 (6.67%) 
Osteoarthritis  1  0/56 (0.00%)  0/35 (0.00%)  1/15 (6.67%) 
Pain in extremity  1  2/56 (3.57%)  1/35 (2.86%)  1/15 (6.67%) 
Nervous system disorders       
Headache  1  7/56 (12.50%)  6/35 (17.14%)  1/15 (6.67%) 
Psychiatric disorders       
Abnormal dreams  1  3/56 (5.36%)  1/35 (2.86%)  0/15 (0.00%) 
Depression  1  3/56 (5.36%)  1/35 (2.86%)  0/15 (0.00%) 
Insomnia  1  4/56 (7.14%)  3/35 (8.57%)  0/15 (0.00%) 
Nervousness  1  0/56 (0.00%)  0/35 (0.00%)  1/15 (6.67%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/56 (1.79%)  2/35 (5.71%)  0/15 (0.00%) 
Sinus congestion  1  2/56 (3.57%)  2/35 (5.71%)  0/15 (0.00%) 
Skin and subcutaneous tissue disorders       
Pruritus  1  2/56 (3.57%)  0/35 (0.00%)  1/15 (6.67%) 
Rash  1  1/56 (1.79%)  0/35 (0.00%)  1/15 (6.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences
EMail: ClinicalTrialDisclosures@gilead.com
Publications of Results:
Wyles D, Brau N, Kottilil S, Daar E, Workowski K, Luetkemeyer A, et al. Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Patients Co-Infected with HCV and HIV-1: The Phase 3 ASTRAL-5 Study [Abstract PS104]. 2016 European Association for the Study of the Liver (EASL), Barcelona, Spain.
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02480712    
Other Study ID Numbers: GS-US-342-1202
First Submitted: June 22, 2015
First Posted: June 24, 2015
Results First Submitted: April 26, 2017
Results First Posted: June 1, 2017
Last Update Posted: November 16, 2018